title: Dietary glycotoxins affect scavenger receptor expression and the hormonal profile of female rats.
abstract: The levels of advanced glycation end products (AGEs) are increased under conditions of impaired glucose metabolism and/or oxidative stress, promoting insulin resistance and other endocrine abnormalities. AGEs play a major role in the pathogenesis of several diseases such as diabetes, atherosclerosis, polycystic ovary syndrome and Alzheimer's disease, contributing to progressive ageing. Receptor-based clearance of AGEs by the receptor for AGE (RAGE) and/or the macrophage scavenger receptor A (SR-A) is considered as a main factor for the regulation of the concentration of AGEs under these conditions. This study aimed to investigate the expression of RAGE (AGER) and SR-A (MSR1) under high/low-dietary AGE conditions in vivo and their potential contribution to the metabolic and sex hormonal profile of female rats. Female Wistar rats were fed a low-AGE or high-AGE diet for 3 months. Serum samples were collected at baseline and at the completion of the 3-month period for the measurements of metabolic and hormonal parameters. Peripheral blood mononuclear cells (PBMCs) were isolated for the determination of the expression of RAGE and SR-A. The high-AGE diet-fed rats exhibited increased glucose, insulin and testosterone levels as well as decreased oestradiol and progesterone levels compared with the low-AGE diet-fed ones, thus indicating a metabolic and hormonal dysregulation attributed to high-AGE dietary exposure. The expression of RAGE was significantly down-regulated in the PBMCs of the high-AGE diet-fed rats (P=0.041), and it was correlated negatively with insulin and testosterone levels and positively with progesterone levels. The expression of SR-A was also decreased in the high-AGE diet-fed rats to marginal significance. Decreased monocytic expression of scavenger receptors such as RAGE and SR-A may result in a higher deposition of AGEs in peripheral endocrine tissues, thus promoting endocrine-related abnormalities and diseases.
authors.affiliation: Department of Experimental Physiology, University of Athens Medical School, Athens, Greece. e.diamanti.kandarakis@gmail.com
authors.forename: Antonios
authors.initials: A
authors.lastname: Chatzigeorgiou
authors.forename: Eleni
authors.initials: E
authors.lastname: Kandaraki
authors.forename: Christina
authors.initials: C
authors.lastname: Piperi
authors.forename: Sarantis
authors.initials: S
authors.lastname: Livadas
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
authors.forename: Apostolos
authors.initials: A
authors.lastname: Papalois
authors.forename: Evanthia
authors.initials: E
authors.lastname: Diamanti-Kandarakis
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects*; D004958:Estradiol / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000633:toxicity; D007328:Insulin / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D011374:Progesterone / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
chemical_list: D017127:Glycation End Products, Advanced; D007328:Insulin; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D005947:Glucose
keywords: AGEs; PCOS; RAGE; SR-A; endocrine dysregulation; insulin resistance